The purpose of this project is to evaluate the carcinogenic potential of medical treatment with drugs. Since many cancer patients are exposed to both radiation and cytotoxic agents, these studies are a logical extension to the Branch's study of radiation-induced second cancers. In addition, other non-therapeutic drugs are studied when of special interest. The Branch also conducts studies of multiple primary cancers to generate hypotheses about host and environmental determinants of specific cancers. Populations under study include cancer patients reported to population- based cancer registries (especially the Surveillance, Epidemiology and End Results [SEER] program), persons treated at major institutions, and those treated in randomized clinical trials. Additional details on collaborative projects can be found in Project No. Z01CP04410-EEB, "Carcinogenic Effects of Therapeutic Drugs" and Project No. Z01CP04410- EEB, "Studies of Persons at High Risk of Cancer." A study of leukemia after breast cancer found the leukemic potential of melphalan to be significantly higher than that for cyclophosphamide. Low but elevated risks were associated with the levels of cyclophosphamide in common use today. Radiation enhanced the risk from alkylating agents. Several studies of patients with non-Hodgkin's lymphoma revealed excesses in second cancers that increased significantly over time. Chemotherapy was strongly related to bladder cancer and leukemia. Immunologic impairment rather than chemotherapy appeared responsible for an increase in second cancer risk among patients with chronic lymphocytic leukemia. Persons with presumed AIDS-related Kaposi's sarcoma had a 200-fold risk of NHL, but only a marginal increase in other tumors. The risk of dying from a second cancer before the age of 40 years is high among children treated for retinoblastoma.